18F-CPFPX PET Identifies Changes in Cerebral A1 Adenosine Receptor Density Caused by Glioma Invasion

Adenosine plays a critical role in both tumor proliferation and the cerebral response to tumor invasion. We used 8-cyclopentyl-3-(3- 1 8 F-fluoropropyl)-1-propylxanthine ( 1 8 F-CPFPX) PET to investigate A 1 adenosine receptor (A 1 AR) density as a potential indicator of the local cerebral response to glioma invasion. Methods: A 1 AR density in F98 glioma-bearing rats was examined by 1 8 F-CPFPX and 3 H-CPFPX using PET, quantitative in vitro and ex vivo double-label receptor autoradiography, and immunohistochemical analyses. Results: For all imaging modalities, A 1 AR signal intensity was increased in a zone surrounding experimental tumors (136%-146% that in control tissue) (P < 0.01). Immunostaining identified activated astrocytes as the main origin of peritumoral A 1 AR upregulation. The results of a pilot 1 8 F-CPFPX PET study on a patient with recurrent glioblastoma multiforme confirmed increases in A 1 AR density in the immediate vicinity of the tumor. Conclusion: 1 8 F-CPFPX PET is suitable for the detection of peritumoral changes in A 1 AR density. Molecular imaging with 1 8 F-CPFPX PET may open novel possibilities for gaining experimental and clinical insights into the cerebral response to tumor invasion.